ABSTRACT. The objective of this study was to compare circulating lipid docosahexaenoic acid [22:6(n-3), DHA] levels in term infants fed a powdered (CORN oil) or liquid (SOY oil) infant formula or human milk (HM). Infants whose mothers chose not to breast feed were randomly assigned to the CORN or SOY formula group. The formula fat differed in linolenic acid [18:3(n-3)] content: it was 0.8% for the CORN and 4.8% for the SOY. Linoleic acid [18:2(n-6)] was 31.5 and 34.2% fatty acids in the CORN and SOY formula, respectively. The formulas or H M were fed from birth through 8 wk of age, and growth and the plasma and red blood cell (RBC) phospholipid fatty acid composition was determined at 3 d, 4 wk, and 8 wk of age. Growth did not differ among groups. The plasma phospholipid and RBC phosphatidylethanolamine DHA was similar in the CORN and SOY formula groups at all ages. Plasma and RBC phosphatidylethanolamine levels of DHA were significantly lower in infants fed the CORN or SOY formula than in infants fed H M during wk 4 and 8. Plasma and RBC 22:5(n-6) was not increased in the formula groups at any age. The formula content of linolenic acid had no effect on the RBC or plasma DHA levels of the infants. The biologic or functional significance of the lower plasma and RBC DHA in infants fed formula rather than H M is unknown. The need for a dietary source of DHA and specificity of plasma or RBC phospholipid DHA as a measure of desaturation and elongation of linolenic acid in developing organs remains uncertain. (Pediatr Res 32: 683-688,1992)

Between May 1993, and September 1994, a randomized, blinded clinical trial was conducted to evaluate measures of growth and body composition in 63 (32 males; 31 females) healthy, low‐birth‐weight infants (940–2250 g) who were randomly assigned to an infant formula with docosahexaenoic acid (22:6n3, DHA, 0.2 wt%) from fish oil or to a control formula. A preterm formula with or without DHA was fed beginning at 7–10 days prior to hospital discharge through 43 weeks postmenstrual age (PMA). Then, from 43‐59 weeks PMA, infants were fed a term infant formula with or without a corresponding amount of DHA. Growth (weight, length, head circumference), regional body fatness (triceps, subscapular, suprailiac skinfold thicknesses), circumferences (arm, abdominal, chest), and estimates of body composition determined by total body electrical conductivity (TOBEC) (fat‐free mass [FFM]) were evaluated. Growth was slower in males fed the DHA formula. They had significantly (P < 0.05) smaller gains in weight, length, and head circumference between study enrollment to 59 weeks PMA than those fed the control formula. At 51 weeks PMA, males in the DHA group had significantly smaller head circumferences (P < 0.05) and lower FFM (P < 0.05). At 59 weeks PMA, males in the DHA group weighed less (P < 0.05), had shorter recumbent lengths (P < 0.01), smaller head circumferences (P < 0.05), and lower FFM (P < 0.01) than those fed the control formula. Energy intakes from formula (kcal/d), however, were lower at 51 weeks (P < 0.05) and 59 weeks (P < 0.05) PMA in males fed the DHA formula. Adjusted for body weight (kcal/kg/d), mean energy intakes from formula at 51 and 59 weeks PMA were not significantly different between feeding groups. The differences in recumbent length, head circumference, and FFM remained statistically significant after controlling for energy and protein intakes (P < 0.01). For all males, neither FFM nor total body fat (TBF), when expressed as a percentage of total body weight, differed significantly between feeding groups. Among females, there were no significant differences between the feeding groups in measures of growth, body composition, or energy intake. The results indicated that infant formula with fish oil containing DHA and EPA in a 5:1 ratio had a significant, negative effect on growth and body composition in males during the first 6 months of life. It is not clear why the growth deficits were limited to males and not females. The eicosanoids, bioactive metabolites of omega‐3 and omega‐6 fatty acids, may mediate several important growth hormones. The present results do not support the addition of DHA alone in infant formulas. Am. J. Hum. Biol. 11:457–467, 1999. © 1999 Wiley‐Liss, Inc.

The effect of fish oil high in docosahexaenoic acid (22:6n-3) and low in eicosapentaenoic acid (20:5n-3) in formula on blood lipids and growth of full-term infants was studied. Infants were fed formula with about 15% oleic acid (18:1), 32% linoleic acid (18:2n-6), 4.9% linolenic acid (18:3n-3) and 0, 0.10, or 0.22% 22:6n-3, or 35% 18:1, 20% 18:2n-6, 2.1% 18:3n-3 and 0, 0.11, or 0.24% 22:6n-3 from 3 d to 16 wk of age (n = 16,18,17,21,17,16, respectively). The formulae had < 0.1% 20:5n-3 and no arachidonic acid (20:4n-6). Breast-fed infants (n = 26) were also studied. Plasma phospholipid and red blood cell (RBC) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) fatty acids were determined at 3 d and 4, 8, and 16 wk of age. These longitudinal analyses showed differences in blood lipid 22:6n-3 between breast-fed and formula-fed infants depending on the feeding duration. At 16 wk, infants fed formula with 0.10, 0.11% 22:6n-3, or 0.22% 22:6n-3 had similar 22:6n-3 levels in the plasma phospholipid and RBC PC and PE compared with breast-fed infants, and higher 22:6n-3 than infants fed formula without 22:6n-3. Formula with 0.24% 22:6n-3, however, resulted in higher plasma phospholipid 22:6n-3 than in breast-fed infants at 16, but not 4 or 8 wk of age. Plasma and RBC phospholipid 20:4n-6 was lower in formula-fed than breast-fed infants, but no differences in growth were found. Higher blood lipid C20 and C22 n-6 and n-3 fatty acids in infants fed formula with 20% 18:2n-6 and 2.4% 18:3n-3 compared with 32% 18:2n-6 and 4.9% 18:3n-3 show the increase in blood lipid 22:6n-3 in response to dietary 22:6n-3 depending on other fatty acids in the formula.